Embryogenesis and gene targeting of coagulation factors in mice

Genetic or acquired thrombophilia of the pregnant mother has been associated with the occurrence of gestational vascular disease and recurrent fetal loss and may contribute to the aetiology of pre-eclampsia. This chapter reviews insights into this link between thrombophilia and pregnancy complications that were gained from the study of genetically altered mice. These studies strongly support the notion of a cause–effect relationship between altered function of the thrombomodulin–protein C pathway and adverse pregnancy outcome. Analysis of the mouse models highlights unique aspects of vascular structure and function at the feto–maternal interface, and exposes new biological functions of natural anticoagulant pathways in pregnancy. These roles are unrelated to the maintenance of vascular patency and may be mediated through specific signalling pathways activated by coagulation factors. Abnormal signalling by placental trophoblasts at the feto–maternal interface is suggested as a hitherto unrecognized mechanism that may underlie adverse pregnancy outcome associated with haemostatic disorders.